title: Replacement of acetate with citrate in dialysis fluid: a randomized clinical trial of short term safety and fluid biocompatibility.
abstract: BACKGROUND
  The majority of bicarbonate based dialysis fluids are acidified with acetate. Citrate, a well known anticoagulant and antioxidant, has been suggested as a biocompatible alternative. The objective of this study was to evaluate short term safety and biocompatibility of a citrate containing acetate-free dialysis fluid.
  
  
  METHODS
  Twenty four (24) patients on maintenance dialysis three times per week, 13 on on-line hemodiafiltration (HDF) and 11 on hemodialysis (HD), were randomly assigned to start with either citrate dialysis fluid (1 mM citrate, 1.5 mM calcium) or control fluid (3 mM acetate, 1.5 mM calcium) in an open-labeled cross-over trial (6 + 6 weeks with 8 treatments wash-out in between). Twenty (20) patients, 11 on HDF and 9 on HD were included in the analyses. Main objective was short term safety assessed by acid-base status, plasma ionized calcium and parathyroid hormone (PTH). In addition, biocompatibility was assessed by markers of inflammation (pentraxin 3 (PTX-3), CRP, IL-6, TNF-α and IL-1β) and thrombogenicity (activated partial thromboplastin time (APTT) and visual clotting scores).
  
  
  RESULTS
  No differences dependent on randomization order or treatment mode (HD vs. HDF) were detected. Citrate in the dialysis fluid reduced the intra-dialytic shift in pH (+0.04 week 6 vs. +0.06 week 0, p = 0.046) and base excess (+3.9 mM week 6 vs. +5.6 mM week 0, p = 0.006) over the study period. Using the same calcium concentration (1.5 mM), citrate dialysis fluid resulted in lower post-dialysis plasma ionized calcium level (1.10 mM vs. 1.27 mM for control, p < 0.0001) and higher post-dialysis PTH level (28.8 pM vs. 14.7 pM for control, p < 0.0001) while pre-dialysis levels were unaffected. Citrate reduced intra-dialytic induction of PTX-3 (+1.1 ng/ml vs. +1.4 ng/ml for control, p = 0.04) but had no effect on other markers of inflammation or oxidative stress. Citrate reduced visual clotting in the arterial air chamber during HDF (1.0 vs. 1.8 for control, p = 0.03) and caused an intra-dialytic increase in APTT (+6.8 s, p = 0.003) without affecting post-dialysis values compared to control.
  
  
  CONCLUSIONS
  During this small short term study citrate dialysis fluid was apparently safe to use in HD and on-line HDF treatments. Indications of reduced treatment-induced inflammation and thrombogenicity suggest citrate as a biocompatible alternative to acetate in dialysis fluid. However, the results need to be confirmed in long term studies.
  
  
  BACKGROUND
  ISRCTN28536511.
authors.affiliation: Gambro Research, Gambro Lundia AB, Lund, Sweden. gunilla.grundstrom@gambro.com.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Grundström
authors.forename: Anders
authors.initials: A
authors.lastname: Christensson
authors.forename: Maria
authors.initials: M
authors.lastname: Alquist
authors.forename: Lars-Göran
authors.initials: LG
authors.lastname: Nilsson
authors.forename: Mårten
authors.initials: M
authors.lastname: Segelmark
mesh_terms: D000085:Acetates / Q000009:adverse effects* / Q000627:therapeutic use; D000138:Acidosis / Q000139:chemically induced / Q000517:prevention & control*; D001672:Biocompatible Materials / Q000009:adverse effects / Q000627:therapeutic use; D019343:Citric Acid / Q000009:adverse effects* / Q000627:therapeutic use*; D015314:Dialysis Solutions / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D006435:Renal Dialysis / Q000009:adverse effects*; D013927:Thrombosis / Q000139:chemically induced / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000085:Acetates; D001672:Biocompatible Materials; D015314:Dialysis Solutions; D019343:Citric Acid